PHARMACOLOGY OF PERIPHERAL NERVOUS SYSTEM.pptx

Pharmacology of peripheral nervous system
Organisation and functions of ANS
Steps involved in neuro humoral transmission
COTRANSMISSION

1. PHARMACOLOGY OF PERIPHERAL NERVOUS SYSTEM SUJI S Assistant professor Dept. Of Pharmacology Holy Grace Academy of Pharmacy, Thrissur

2. NERVOUS SYSTEM The nervous system is a complex network of nerves and cells that carry messages to and from the brain and spinal cord to various parts of the body. Nervous system along with endocrine system is responsible for the maintenance of homeostasis in the body. The nervous system includes the central nervous system (CNS) and peripheral nervous system (PNS). The CNS is made up of the brain and spinal cord, whereas the PNS is made up of the somatic and autonomic nervous systems.

3. Somatic Nervous System The main function of the somatic nervous system is to transfer impulses from CNS to skeletal muscles.It consists of 1. Cranial Nerves 2. Spinal Nerves Cranial nerves are 12 pairs and they emerge from the brain. Some of the examples of cranial nerves are optic, olfactory, etc. Spinal nerves have their point of emergence as the spinal cord. There are 31 pairs of spinal nerves. They emerge from the spinal cords into dorsal and ventral roots

4. Organisation and functions of ANS The ANS controls unconscious visceral actions The autonomic nervous system is organized into two branches, the sympathetic nervous system (SNS) and the parasympathetic nervous system (PSNS). sympathetic nervous system consists of nerves arising from the spinal cord between the neck and waist region. It prepares the body for violent actions against abnormal conditions and is generally stimulated by adrenaline. parasympathetic nervous system is located anterior in the head and neck and posterior in the sacral region. It is mainly involved in the re-establishment of normal conditions when violent action is over. acetylcholine is the main neurotransmitter.

5. NEUROTRANSMITTER Neurotransmitters are chemical agents which allow transmission of signals from one nerve cell to the other nerve cell across a synapse. Neurotransmitters are packaged into synaptic vesicles - presynaptic side of a synapse.

6. CLASSIFICATION OF NEUROTRANSMITTERS Physiological

7. Biochemical

8. ACETYLCHOLINE Acetylcholine was the first neurotransmitter to be discovered. Use choline as a precursor - cholinergic neurotransmitter. Used by the Autonomic Nervous System, such as smooth muscles of the heart, as an inhibitory neurotransmitter. Responsible for stimulation of muscles, including the muscles of the gastro-intestinal system. Related to Alzheimer's Disease.

9. Dopamine Is synthesized in three steps from the amino acid tyrosine. Generally involved in regulatory motor activity, in mood, motivation and attention. Schizophrenics have too much dopamine. Patients with Parkinson's Disease have too little dopamine.

10. NOREPINEPHRINE (nor adrenaline) Synthesized directly from dopamine. It is synthesized from tyrosine. Norepinephrine is strongly associated with bringing our nervous systems into "high alert." It increases our heart rate and our blood pressure. It is also important for forming memories.

11. GLUTAMATE It is an amino acid It the most commonly found excitatory neurotransmitter in the brain. It is involved in most aspects of normal brain function including cognition, memory and learning. Glutamate is formed from α – ketoglutarate, an intermediate of Kreb’s cycle.

12. SEROTONIN (5-HT) Synthesized from the amino acid tryptophan Regulates attention and other complex cognitive functions, such as sleep (dreaming), eating, mood, pain regulation. Too little serotonin has been shown to lead to depression, anger control etc

13. NEUROHUMORAL TRANSMISSION Neurohumoral transmission is the transmission of a nerve impulse from a presynaptic to a postsynaptic neuron that passes through a humoral substance like a biogenic amine, an amino acid, or a peptide. STEPS Impulse conduction Transmitter Release Transmitter action on post junctional membrane Post junctional activity Termination of transmitter action

14. Impulse conduction

15. Resting transmembrane potential -70mv (inside) (High concentration K+ ion). Electrical impulse causes increase in Na+ conductance so depolarization occur. voltage become +20mv. K+ ion then move out in the direction of their concentration and repolarization achieved. The action potential thus generated set of local circuit currents which active ionic channel at the next excitable part of the membrane.

16. 2) Transmitter Release Nerve impulses leads to opening of voltage sensitive Ca2+ channels Ca2+ helps in fusion between axoplasmic membrane and synaptic vesicles Neurotransmitter release by endocytosis.

17. 3) Transmitter action on post junctional membrane Release transmitter combine with specific receptor on post junctional membrane and depending on its nature induce an excitatory postsynaptic potential (EPSP) or inhibitory post-synaptic potential (IPSP.) EPSP ncrease permeability of cations, so that Na+ Ca2+ influx IPSP Increase permeability of anions (Cl– ion move inside)

18. 4) Post junctional activity

19. EPSP: propagated post junctional AP results nerve impulse secretions. IPSP: stabilize the post junctional membrane. It resist depolarization stimuli.

20. 5) Termination of transmitter action

21. CHOLINERGIC TRANSMISSION Biosynthesis Choline is transported into the presynaptic cholinergic nerve terminal by a high-affinity Na-choline co-transporter. This transporter is inhibited by hemicholinium . The cytosolic enzyme choline acetyltransferase catalyzes the formation of acetylcholine (ACh) from acetyl coenzyme A (AcCoA) and choline.

22. 2) Storage and release Newly synthesized ACh is packaged (together with ATP and proteoglycans) into vesicles for storage. Transport of ACh into the vesicle is mediated by a H-ACh antiporter, which is inhibited by vesamicol . When an action potentials arrives at the nrve terminal, voltage sensitive Ca2+ channels open.The ACh-containing vesicles fuse with the plasma membrane when intracellular calcium levels increase. This will leads to releasing of neurotransmitter into the synaptic cleft. Botulinum toxin prevents the exocytosis of presynaptic vesicles, thereby blocking ACh release.

23. 3) Binding to the Receptors Acetylcholine diffuses in the synaptic cleft and binds to postsynaptic and presynaptic receptors. Acetylcholine receptors are divided into nicotinic and muscarinic receptors. Nicotinic receptors are ligand-gated ion channels that are permeable to cations Muscarinic receptors are G protein-coupled receptors that alter cell signaling pathways, including activation of phospholipase C (PLC), inhibition of adenylyl cyclase (AC), and opening of K channels. Postsynaptic nicotinic receptors and M1, M3, and M5nmuscarinic receptors are excitatory, postsynaptic M2 and M4 muscarinic receptors are inhibitory.

24. 4) Metabolism or Termination of action Acetylcholine in the synaptic cleft is degraded by membrane-bound acetylcholinesterase (AChE) into choline and acetate . Numerous inhibitors of AChE exist; most clinically relevant anticholinesterases are competitive inhibitors of the enzyme

25. ADRINERGIC TRANSMISSION Biosynthesis Nonepinephrine is biosynthesized by the active transport of L-tyrosine into adrenergic neurons. Then it is hydroxylated to Dihydroxyphenyalanine ( DOPA ) by the enzyme tyrosine hydroxylase This step is the rate limiting step (Slowest step) in the formation of epinephrine. Dopa is decarboxylated to form dopamine in presence of enzyme DOPA decarboxylase in the synaptic neurons

26. STORAGE Dopamine is then transported into synaptic vesicles by an amine transport system This transport carrier is blocked by Reserpine . Dopamine hydroxylated to form Nor-epinephrine in presence of enzyme β-hydroxylase. The CAs and other co-transmitters (DA, NE, ATP, β-hydroxylase etc.) are stored as a complex with ATP. NEs Methylated to form epinephrine

27. 2) RELEASE Action potential arise at the nerve junction and trigger the Ca2+ ions into the cytoplasm of neuron. Increase concentration of Ca2+ ion causes fuse cell membrane and to undergo exocytosis. Guanithidine block this release. 3) BINDING TO REC EPTORS NE released from the sympathetic vesicle diffuse into synaptic space and binds to post synaptic receptors.

28. 4) UPTAKE Axonal Uptake: • Take up NE is higher affinity than E and had be called as uptake-01. NET is present at neuronal membrane which transport NE by Na+ coupled mechanism. •This uptake is most important mechanism for terminating the post junctional action of NA. •This pump is inhibited by Cocaine, Imipramine, Desipramine and others. b) Vesicular Uptake : • Vesicular monoamine transporter (VMAT-2) which transport CAs . . from the cytoplasm to the interior of the storage vesicle.

29. 5) METABOLISM Releasing of NE from vesicles into cytoplasm as well as taken up by axonal transport is attached with Mono amine oxidase (MAO) and Catechol-O-M-transferase (COMT) in liver and other tissue.

30. COTRANSMISSION Neurons release more than one transmitter or modulator each of which interacts with specific receptors and produces effects both pre and postsynaptically The cotransmitter is stored in the prejunctional nerve terminal alongwith the primary transmitter, but in separate vesicles (in some cases in the same vesicle itself Nerve impulse releases both the transmitters concurrently. Act on its own receptors, the cotransmitter modifies responsiveness of the effector to the primary transmitter or substitutes for it. Cotransmitter may also act on prejunctional receptors and modulate release of the transmitter

31. In the ANS, besides the primary transmitters ACh and NA, neurones have been found to elaborate purines (ATP, adenosine), peptides (vasoactive intestinal peptide or VIP, neuropeptideY or NPY, substance P, enkephalins, somatostatin, etc.), nitric oxide and prostaglandins as cotransmitters In most autonomic cholinergic neurones VIP is associated with ACh , while ATP is associated with both ACh and NA.

32. Neuropeptide Y (NPY) ✓ NPY is co-released with NE in sympathetic nerves and it causes constriction of blood vessels . ✓ NPY also exerts prejunctional modulatory effects on transmitter release and synthesis Vasoactive Intestinal Peptide(VIP) ✓ Vasoactive Intestinal Peptide (VIP) co-released with ACh parasympathetic division of autonomic nerves system. ✓ VIP regulates the secretions of saliva during cholinergic stimulation and it partly contributes in vasodilation . ✓ VIP may be involved in parasympathetic responses in trachea and in the GI tract .

33. 3) Substance P : It is co-transmitter with acetylcholine. Substance P released from sensory nerves and it mediate inflammation , it includes airway smooth muscle contraction . It can cause vasodilatation